BioEssays

Published by Wiley-VCH Verlag
Online ISSN: 1521-1878
Print ISSN: 0265-9247
Publications
Setting optimal significance levels that minimize Type I and Type II errors allows for more transparent and well-considered statistical decision making compared to the traditional α = 0.05 significance level. We use the optimal α approach to re-assess conclusions reached by three recently published tests of the pace-of-life syndrome hypothesis, which attempts to unify occurrences of different physiological, behavioral, and life history characteristics under one theory, over different scales of biological organization. While some of the conclusions reached using optimal α were consistent to those previously reported using the traditional α = 0.05 threshold, opposing conclusions were also frequently reached. The optimal α approach reduced probabilities of Type I and Type II errors, and ensured statistical significance was associated with biological relevance. Biologists should seriously consider their choice of α when conducting null hypothesis significance tests, as there are serious disadvantages with consistent reliance on the traditional but arbitrary α = 0.05 significance level.
 
Recent studies have yielded new insights into the critical importance of adequate vitamin D 3 intake and metabolism. Investigations of the actions of 1,25-dihydroxyvitamin D 3 (calcitriol) on novel target tissues has revealed that this hormone has functions other than its recognized action in regulating blood calcium and phosphate levels. Reports have characterized calcitriol receptors and activities in organs and tissues as diverse as pancreas, skeletal and heart muscle, blood cells, brain, skin, pituitary, parathyroid, kidney, bone and intestine. These studies suggest functions for calcitriol as varied as the regulation of insulin and prolactin secretion, muscle contractility, immune cell metabolism, melanin synthesis and differentiation of blood cells. This information may ultimately help us to understand the etiologies of several kinds of organ dysfunction and lead to the development of tissue-specific agents for new therapies. Peer Reviewed http://deepblue.lib.umich.edu/bitstream/2027.42/50182/1/950040206_ftp.pdf
 
beta 1,4-galactosyltransferase is unusual among the glycosyltransferases in that it is found in two subcellular compartments where it performs two distinct functions. In the trans-Golgi complex, galactosyltransferase participates in oligosaccharide biosynthesis, as do the other glycosyltransferases. On the cell surface, however, galactosyltransferase associates with the cytoskeleton and functions as a receptor for extracellular oligosaccharide ligands. Although we now know much regarding galactosyltransferase function in these two compartments, little is known about how it is targeted to these different sites. By cloning the galactosyltransferase gene products, certain features of the protein have been identified that may be critical for its expression on the cell surface or retention within the Golgi complex. This article discusses recent studies which suggest that a cytoplasmic sequence unique to one galactosyltransferase isoform is required for targeting a portion of this protein to the plasma membrane, enabling it to function as a cell adhesion molecule. These findings allow one to manipulate surface galactosyltransferase expression, either positively or negatively, and perturb galactosyltransferase-dependent cellular interactions during fertilization and development.
 
The cellular slime mold Dictyostelium has cell-cell connections similar in structure, function, and underlying molecular mechanisms to animal epithelial cells. These similarities form the basis for the proposal that multicellularity is ancestral to the clade containing animals, fungi, and Amoebozoa (including Dictyostelium): Amorphea (formerly "unikonts"). This hypothesis is intriguing and if true could precipitate a paradigm shift. However, phylogenetic analyses of two key genes reveal patterns inconsistent with a single origin of multicellularity. A single origin in Amorphea would also require loss of multicellularity in each of the many unicellular lineages within this clade. Further, there are numerous other origins of multicellularity within eukaryotes, including three within Amorphea, that are not characterized by these structural and mechanistic similarities. Instead, convergent evolution resulting from similar selective pressures for forming multicellular structures with motile and differentiated cells is the most likely explanation for the observed similarities between animal and dictyostelid cell-cell connections.
 
In a recent paper, Merabet and Hudry discuss models explaining the functional evolution of fushi tarazu (ftz) from an ancestral homeotic to a pair-rule segmentation gene in Drosophila. As most of the experimental work underlying these models comes from our research, we wish to reply to Merabet and Hudry providing an explanation of the experimental approaches and logical framework underlying them. We review experimental data that support our hypotheses and discuss misconceptions in the literature. We emphasize that the change in ftz function required changes in both expression pattern and protein function and review the evidence that these functional changes involved a switch in cofactor-interaction motifs during arthropod radiations. While agreeing with Merabet and Hudry that protein context likely contributes to Ftz function, we argue that until supporting evidence for alternative mechanisms is obtained, the role of cofactor-interaction motifs in driving a functional switch remains compelling.
 
This is a commentary on article Laurent R, Chaix R. MHC-dependent mate choice in humans: why genomic patterns from the HapMap European American dataset support the hypothesis. Bioessays. 2007;34(4):267-71.
 
Response/Comment on the SMT theory as defined by David L Vaux (DOI: 10.1002/bies.201100022) by Soto & Sonnenschein
 
Meiosis is the process by which diploid germ cells divide to produce haploid gametes for sexual reproduction. The process is highly conserved in eukaryotes, however the recent availability of mouse models for meiotic recombination has revealed surprising regulatory differences between simple unicellular organisms and those with increasingly complex genomes. Moreover, in these higher eukaryotes, the intervention of physiological and sex-specific factors may also influence how meiotic recombination and progression are monitored and regulated. This review will focus on the recent studies involving mouse mutants for meiosis, and will highlight important differences between traditional model systems for meiosis (such as yeast) and those involving more complex cellular, physiological and genetic criteria.
 
c-Jun N-terminal kinases (JNKs) are intracellular stress-activated signalling molecules, which are controlled by a highly evolutionarily conserved signalling cascade. In mammalian cells, JNKs are regulated by a wide variety of cellular stresses and growth factors and have been implicated in the regulation of remarkably diverse biological processes, such as cell shape changes, immune responses and apoptosis. How can such different stimuli activate the JNK pathway and what roles does JNK play in vivo? Molecular genetic analysis of the Drosophila JNK gene has started to provide answers to these questions, confirming the role of this molecule in development and stress responses and suggesting a conserved function for JNK signalling in processes such as wound healing. Here, we review this work and discuss how future experiments in Drosophila should reveal the cell type-specific mechanisms by which JNKs perform their diverse functions.
 
Ideas about the mechanisms that regulate chromosome pairing, recombination, and segregation during meiosis have gained in molecular detail over the last few years. The purpose of this article is to survey briefly the shifts in paradigms and experiments that have generated new perspectives. It has never been very clear what it is that brings together the homologous chromosomes at meiotic prophase. For a while it appeared that the synaptonemal complex might be the nuclear organelle responsible for synapsis, but the supporting evidence has not been entirely convincing. Whatever the mechanism, it has always been assumed that homologous synapsis creates the opportunity for homologous DNA sequences to initiate recombination. At present, alternative ideas are developing. Attractive is the concept that double strand DNA repair mechanisms, that find and use the undamaged homologue for repair, have evolved into a meiotic mechanism for the recognition and pairing of homologous sequences. Subsequent intimate synapsis of homologous chromosomes in the context of the synaptonemal complex may serve later functions in the regulation of interference and segregation at first anaphase. A number of areas that are being tested at present and some that may be investigated in the future are discussed at the end of the review.
 
Since its discovery as a protein associated with the cytoplasmic region of E-cadherin, beta-catenin has been shown to perform two apparently unrelated functions: it has a crucial role in cell-cell adhesion in addition to a signaling role as a component of the Wnt/wg pathway. Wnt/wg signaling results in beta-catenin accumulation and transcriptional activation of specific target genes during development. It is now apparent that deregulation of beta-catenin signaling is an important event in the genesis of a number of malignancies, such as colon cancer, melanoma, hepatocellular carcinoma, ovarian cancer, endometrial cancer, medulloblastoma pilomatricomas, and prostate cancer. beta-catenin mutations appear to be a crucial step in the progression of a subset of these cancers, suggesting an important role in the control of cellular proliferation or cell death. The APC/beta-catenin pathway is highly regulated and includes players such as GSK3-beta, CBP, Groucho, Axin, Conductin, and TCF. c-MYC and cyclin D1 were recently identified as a key transcriptional targets of this pathway and additional targets are likely to emerge. Published 1999 John Wiley & Sons, Inc.
 
E4BP4, a mammalian basic leucine zipper (bZIP) transcription factor, was first identified through its ability to bind and repress viral promoter sequences. Subsequently, E4BP4 and homologues in other species have been implicated in a diverse range of processes including commitment to cell survival versus apoptosis, the anti-inflammatory response and, most recently, in the mammalian circadian oscillatory mechanism. In some of these cases at least, E4BP4 appears to act antagonistically with members of the related PAR family of transcription factors with which it shares DNA-binding specificity. This diversity of function is mirrored by the regulatory pathways impinging on E4BP4, which include regulation by ras via the lymphokine IL-3 in murine B-cells, by thyroid hormone during Xenopus tail resorption, by glucocorticoids in murine fibroblasts and by calcium in rat smooth muscle cells. This article will cover the unfolding role/s of and regulation of E4BP4, E4BP4-like proteins and PAR factors in species as diverse as mouse and C. elegans.
 
Temporal estimation data from humans (A, B) or rats (C, D) using peak-interval timing procedures. In the peak-interval procedure used with humans, participants were instructed to watch as a blue square appeared on a computer screen and to be " aware " of the amount of time that passed (either 8,12, or 21sec) before the square changed color (the criterion duration). After several training trials, participants were instructed that the blue square would appear for an indefinite amount of time, and that they should indicate when in time they expected the square to change by pressing the spacebar. In 25% of the trials, the participants were advised as to whether they were " too early, " " too late, " or " correct. " In all trials, the participants were instructed not to count or subdivide the duration in any fashion. (A) Shows the times of the spacebar presses for each duration, tested successively. Participants temporal estimations are quite accurate in that their responses were most likely to contain the criterion times. Furthermore, the probability of these responses increased up to the criterion time and decreased in a nearly symmetrical manner following the criterion time. Notice, however, that the spread of responses are considerably broader for the 21 sec duration than for the 8 sec duration. (B) When the temporal response functions are normalized by the criterion time, they superimpose. In other words, they have a constant coefficient of variation, indicative of a multiplicative scaling of a temporal percept as duration changes. This broadening of the response function is the scalar property of interval timing. These data were reprinted by permission from Rakitin et al. (75) . In the lower half of the figure is a similar experiment using rats. Rats were trained to press a specific duration-paired lever for food reward, which would be delivered on 50% of the trials for the first press after the criterion duration (30 or 90 sec) following the onset of a tone. In contrast to the human experiment, the rats were not instructed which duration to time, and switched from responding primarily on the 30 sec lever to responding primarily on 90 sec lever as the trial elapsed. (C) The presses on each lever in unreinforced probe trials. Again, the data show that the rats are accurate, although less precise than humans, at timing these intervals. (D) shows the scalar property for these data, after normalizing the temporal response functions by the criterion times. Data in (C) and (D) are from unpublished research conducted in our laboratory.  
Models and Mechanisms of Interval Timing
All internal clock models require three primary stages or components: clock, memory, and comparison. The clock component usually entails a substrate that changes with time, and sometimes a separate mechanism that accumulates or evaluates the changing substrate. Upon reinforcement or feedback, the value in the clock stage is stored in reference memory so that the temporal information may be used to predict future expectancies. The decision or comparison stage operates by comparing the current clock reading to the previously stored duration memories, and when these two values cross a similarity threshold, the subject is presumed to initiate a " time's up " response.  
This simulation of 100 striatal neurons shows a clear increase and decrease in activity as the time approaches the trained criterion duration of 10 sec. The peaks of activity at the harmonics of the duration (e.g., at 2.5, 5, 7.5, . . . sec) that occur in the beat frequency model have been eliminated in the current model by incorporating biological constraints, such as variance within and between trials in both oscillation speed and spike threshold, as well as by instituting a dynamic bistable membrane potential in the striatal neuron.  
Interval timing in the seconds-to-minutes range is believed to underlie a variety of complex behaviors in humans and other animals. One of the more interesting problems in interval timing is trying to understand how the brain times events lasting for minutes with millisecond-based neural processes. Timing models proposing the use of coincidence-detection mechanisms (e.g., the detection of simultaneous activity across multiple neural inputs) appear to be the most compatible with known neural mechanisms. From an evolutionary perspective, coincidence detection of neuronal activity may be a fundamental mechanism of timing that is expressed across a wide variety of species. BioEssays 22:94-103, 2000.
 
During meiosis, homologous chromosomes must pair in order to permit recombination and correct chromosome segregation to occur. Two recent papers show that meiotic pairing is also important for correct gene expression during meiosis. They describe data for the filamentous fungus Neurospora crassa that show that a lack of pairing generated by ectopic integration of genes can result in silencing of genes expressed during meiosis. This can result in aberrant meioses whose defects are specific to the function of the unpaired gene. Furthermore, mutations affecting the silencing mechanism have been selected in a gene encoding a putative RNA-dependent RNA polymerase. This finding indicates the involvement of a meiotic specific post-transcriptional gene silencing mechanism (PTGS) similar to that observed in vegetative cells in N. crassa and other organisms. Finally, this gene product is essential for normal meiosis, suggesting that RNA-dependent processes are fundamental to the sexual cycle.
 
The contractile vacuole (CV) is an osmoregulatory organelle whose mechanisms of function are poorly understood. Immunological studies in the last decade have demonstrated abundant proton-translocating V-type ATPases (V-ATPases) in its membrane that could provide the energy, from proton electrochemical gradients, for moving ions into the CV to be followed by water. This review emphasizes recent work on the contractile vacuole complex (CVC) of Paramecium including (1) CV expulsion, (2) a role for V-ATPases in sequestering fluid, (3) identifying ions in the cytosol and in the CV, (4) in situ electrophysiological parameters of the CVC membrane, and (5) a better understanding of the membrane dynamics of this organelle.
 
Top-cited authors
Brian K Hall
  • Dalhousie University
William Martin
  • Heinrich-Heine-Universität Düsseldorf
Ronald Koes
  • University of Amsterdam
Francesca Quattrocchio
  • University of Amsterdam
Nick Lane
  • University College London